Newborn screening for severe combined immunodeficiency and T‐cell lymphopenia

Abstract

Summary The development of a T cell receptor excision circle (TREC) assay utilizing dried blood spots made possible universal newborn screening (NBS) for severe combined immunodeficiency (SCID) as a public health measure. Upon being flagged by an abnormal screening test in a SCID screening program, an infant can receive further diagnostic testing for SCID in the neonatal period, prior to onset of infectious complications, to pemit immediate institution of protective measures and definitive, life-saving treatment to establish a functional immune system. SCID screening is now the accepted standard of care in state public health departments across the USA, and it is being adopted in many countries. It has proven effective, with infants having this otherwise inapparent but serious, rare disorder achieving survival and immune reconstitution. In addition to bringing to attention infants with the primary screening target diseases, typical SCID and leaky SCID (due to hypomorphic mutations in known SCID genes), the newborn screening assay for insufficient TRECs in dried blood spots also reveals infants with non-SCID T lymphopenic conditions. Experience has accumulated regarding the range and limitations of diagnoses of newborns with low TRECs and low T cells. Previously unknown immune defects have been discovered, as well as conditions not formerly recognized to have low T cells in the neonatal period.

Haematopoietic stem cell transplantation for inborn errors of immunity: 25‐year experience from University of Malaya Medical Centre, Malaysia

“…In resource‐limited settings, HLA‐haploidentical HSCT using the T‐cell replete post‐transplant cyclophosphamide approach offers accessibility of this procedure to children with IEI who lack a matched donor. Delays in diagnosis remains a major obstacle in achieving better overall outcomes for patients with IEI, the former may be addressed by the implementation of a nationwide neonatal screening program as practiced in some countries . With expanding resources and improvements in transplant technology, the future of HSCT for IEI in Malaysia appears promising.…”

“…Delays in diagnosis remains a major obstacle in achieving better overall outcomes for patients with IEI, the former may be addressed by the implementation of a nationwide neonatal screening program as practiced in some countries. 18 With expanding resources and improvements in transplant technology, the future of HSCT for IEI in Malaysia appears promising.…”

Latin American consensus on the supportive management of patients with severe combined immunodeficiency

“…4 Given that SCID is rare and usually asymptomatic at birth, population-based newborn screening (NBS) using a T-cell receptor DNA excision circle assay on dried blood spots is currently a useful strategy to identify patients with SCID earlier and before the development of infectious complications. 5 Universal NBS has been implemented in the United States and some other regions but is still not a reality in most parts of the world. 5,6 TREATMENT AND PROGNOSIS Curative treatments for SCID depending on the molecular defect and availability are hematopoietic stem cell transplantation (HSCT) or gene therapy.…”

Introduction: Continuing insights into the healthy and diseased immune system through human genetic investigation

“…Finally, some monographs address specific components of the immune system, such as NK cells, tissue neutrophils, and regulatory T cells . Finally, we have a critical assessment of how clinical molecular advances are brought into the realm of public health by perinatal testing for T cell receptor excision circles or TRECs …”

“…20 Finally, we have a critical assessment of how clinical molecular advances are brought into the realm of public health by perinatal testing for T cell receptor excision circles or TRECs. 21 Genetic defects underlying disease seem to follow Murphy's law, "Whatever can go wrong, will go wrong." At the most fundamental level, humans are hostages and beneficiaries, as all organisms, to imperfections in the fidelity of DNA replication and repair.…”